Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons.
Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons.
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DOI：
10.7554/elife.59799
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发表时间：
2020-08-28
期刊：
影响因子：
7.7
通讯作者：
Palmiter RD
中科院分区：
文献类型：
--
作者：
Bowen AJ;Chen JY;Huang YW;Baertsch NA;Park S;Palmiter RD
臂旁CGRP神经元接收不同的威胁相关信号，参与小鼠适应性威胁反应的多个阶段，它们的失活既减弱了对躯体疼痛的无条件行为反应，也减弱了恐惧记忆的形成。由于CGRPPBN神经元广泛地对多模式威胁做出反应，目前尚不清楚这些不同的适应过程是如何单独参与的。我们发现，当CGRPPBN神经元的三个部分分离的子集广泛地侧支到它们各自的下游伙伴时，单独的投射完成不同的功能：下丘脑和延伸的杏仁核投射引发包括自主神经唤醒、焦虑和冻结行为在内的各种无条件威胁反应，而丘脑和基础前脑投射产生冻结行为，并且出人意料地有助于联想恐惧学习。此外，个体投射产生的无条件反应是互补的，多个部位的同时激活导致了严重的冰冻行为和心动过缓，这是任何个体投射都不会引发的。这种半并行、可扩展的连接方案可能有助于在不可预测的环境中灵活控制威胁响应。
Parabrachial CGRP neurons receive diverse threat-related signals and contribute to multiple phases of adaptive threat responses in mice, with their inactivation attenuating both unconditioned behavioral responses to somatic pain and fear-memory formation. Because CGRPPBN neurons respond broadly to multi-modal threats, it remains unknown how these distinct adaptive processes are individually engaged. We show that while three partially separable subsets of CGRPPBN neurons broadly collateralize to their respective downstream partners, individual projections accomplish distinct functions: hypothalamic and extended amygdalar projections elicit assorted unconditioned threat responses including autonomic arousal, anxiety, and freezing behavior, while thalamic and basal forebrain projections generate freezing behavior and, unexpectedly, contribute to associative fear learning. Moreover, the unconditioned responses generated by individual projections are complementary, with simultaneous activation of multiple sites driving profound freezing behavior and bradycardia that are not elicited by any individual projection. This semi-parallel, scalable connectivity schema likely contributes to flexible control of threat responses in unpredictable environments.